Is TEK p.Val78Ala (c.233T>C) pathogenic?

TEK p.Val78Ala (c.233T>C) is classified Benign in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-31). AlphaMissense: likely benign (0.0767); Ultra-rare (popmax 0.0853%, afr).

How common is TEK p.Val78Ala (c.233T>C) in the general population?

TEK p.Val78Ala (c.233T>C) is ultra-rare (popmax 0.0853%, afr) (gnomAD).

What do computational predictors say about TEK p.Val78Ala (c.233T>C)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

TEK p.Val78Ala

c.233T>C · rs146302981 · VCV2884778

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0853%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.44	GERP -3
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	6.267	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0853% African / African-American · 64/75,040 alleles

Filtering AF 0.0685% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0624%

Overall 0.00446% 72/1,614,176 alleles · ultra-rare exomes 33/1,461,878 · genomes 39/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0853%	1,173
Admixed American	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.0048%	20,836

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TEK
Protein: p.Val78Ala
Coding: c.233T>C
MANE Select: NM_000459
dbSNP: rs146302981
Type: single nucleotide variant
Location: chr9:27158011 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 78: a UniProt-annotated variant site (in glc3e; formation of protein aggregates); the ig-like c2-type 1 domain

Full TEK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TEK p.Val78= Benign ★★ same residue
TEK p.Val78Met Uncertain significance ★ ⚠ same residue
TEK p.Arg1099Ter Pathogenic ★★ same type
TEK p.Arg849Trp Pathogenic ★★ ⚠ same type
TEK p.Arg915Cys Pathogenic/Likely pathogenic ★★ same type
TEK p.Arg915His Pathogenic/Likely pathogenic ★★ same type
TEK p.Arg918Cys Pathogenic/Likely pathogenic ★★ same type
TEK p.Gln518Ter Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tek-p-val78ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown